Objective: To review the progress in the field of MHC-related genetic susceptibility to Behçet's disease (BD).
Method: Systematic review of the English literature between 1 January 1980 and 31 January 2010 using Medline. Case-control, population-based, observational cohort studies investigating the association between BD and HLA-B*51 subtypes, classical and non-classical HLA alleles and other HLA-related genes were selected. The geographical distribution of BD and these susceptibility genes was also taken into consideration. Case and familial case reports were excluded except for case series with more than two patients.
Results: Ninety articles plus 17 obtained from other sources were included in the systematic review. We have found high evidence that a core component of genetic susceptibility to BD is within the MHC region being primarily related to an HLA-B*51 subtype: HLA-B*5101/B*510101. Moreover, HLA-A*26, HLA-B*15, HLA-B*5701 and TNF-α -1031C were independently associated with BD. Data suggest that other HLA (HLA-C, HLA-DR) and HLA-related [MHC Class I chain-related gene A (MIC-A), TNF-α] genes may play a role in BD co-susceptibility or pathogenesis. Finally, the distinctive geographical distribution of BD suggested an evolutionary selection of HLA-B*51 subtypes as the major susceptibility factors for BD.
Conclusion: Further studies must be addressed to clarify the functional relevance of the different genes found to be associated with disease susceptibility and the potential interactions between genes located within and outside the MHC region.